Studies on the mechanisms of bronchogenic carcinoma induction by chemical and physical factors, alone or in various combinations of factors, are pursued in the hamster respiratory carcinogenesis model (Saffiotti, l968). In vivo studies use two newly established Syrian golden hamster colonies: inbred 15:16/Bio. EHS and outbred Syrian /CG.FOD. Treatments include: intratracheal instillation of carcinogens absorbed on particulate carriers, alone or in combinations; systemic vs. topical treatments; and combined treatments with carcinogens and cofactors. Respiratory epithelial tissue responses are characterized by histological, histochemical and biochemical methods, and by their study in organ and cell culture condition. Long-term studies were completed on the topical effects of N-methyl-N-nitrosourea which resulted in the unusual induction of spindle-cell carcinomas and on 2,6-dimethyl-nitrosomorpholine which induced a variety of tumor types located in all segments of the respiratory tract.